Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
University of Milano-Bicocca, Milan, Italy.
Nephrol Dial Transplant. 2020 Sep 1;35(9):1518-1526. doi: 10.1093/ndt/gfz150.
Despite long-standing clinical use of sodium polystyrene sulphonate (SPS) for hyperkalaemia management in chronic kidney disease (CKD), its safety profile remains poorly investigated.
We undertook an observational analysis of nephrology-referred adults with incident CKD Stage 4+ in Sweden during 2006-16 and with no previous SPS use. We studied patterns of use and adverse events associated to SPS initiation during follow-up. Patterns of SPS use were defined by chronicity of treatment and by prescribed dose. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) associated with SPS initiation (time-varying exposure) for the risk of severe (intestinal ischaemia, thrombosis or ulceration/perforation) and minor (de novo dispensation of laxatives or anti-diarrheal drugs) gastrointestinal (GI) events.
Of 19 530 SPS-naïve patients with CKD, 3690 initiated SPS during follow-up. A total of 59% took SPS chronically, with an average of three dispensations/year. The majority (85%) were prescribed lower dosages than specified on the product label. During follow-up, 202 severe and 1149 minor GI events were recorded. SPS initiation was associated with a higher incidence of severe adverse events [adjusted HR 1.25 95% CI 1.05-1.49)], particularly in those receiving per label doses [1.54 (1.09-2.17)] and mainly attributed to ulcers and perforations. SPS initiation was also associated with higher incidence of minor GI events [adjusted HR 1.11 (95% CI 1.03-1.19)], regardless of dose, and mainly accounted for by de novo dispensation of laxatives.
Initiation of SPS in patients with advanced CKD is associated with a higher risk of severe GI complications as well as the initiation of GI-related medications, particularly when prescribed at per label doses.
尽管聚苯乙烯磺酸鈉(SPS)在慢性肾脏病(CKD)高钾血症管理中已有长期的临床应用,但对其安全性仍缺乏深入研究。
我们对 2006 年至 2016 年期间瑞典新诊断为 CKD 4 期及以上且既往未使用过 SPS 的肾病科患者进行了观察性分析。我们研究了 SPS 起始治疗与随访期间相关不良事件的使用模式。SPS 的使用模式由治疗的慢性和处方剂量定义。我们估计了 SPS 起始治疗(时变暴露)与严重(肠道缺血、血栓形成或溃疡/穿孔)和轻微(新处方缓泻剂或止泻药)胃肠道(GI)事件风险相关的风险比(HR)和 95%置信区间(CI)。
在 19530 例 SPS 初治 CKD 患者中,有 3690 例患者在随访期间开始使用 SPS。总共 59%的患者长期服用 SPS,每年平均处方 3 次。大多数患者(85%)的处方剂量低于产品标签上的规定剂量。在随访期间,共记录到 202 例严重和 1149 例轻微的 GI 不良事件。SPS 起始治疗与严重不良事件的发生率较高相关[校正 HR 1.25,95%CI 1.05-1.49],特别是在接受标签剂量治疗的患者中[1.54(1.09-2.17)],主要与溃疡和穿孔有关。SPS 起始治疗也与轻微的 GI 不良事件的发生率较高相关[校正 HR 1.11(95%CI 1.03-1.19)],无论剂量如何,主要与新处方缓泻剂有关。
在晚期 CKD 患者中起始 SPS 治疗与严重 GI 并发症以及与 GI 相关药物的起始治疗相关,尤其是在按标签剂量治疗时风险更高。